2-Amino-4-fluorobenzamide → 7-Fluoro-3,4-dihydro-1,2,3-benzotriazin-4-one

HRID 714761

Reaction equation

HRID 714761 reaction equation
[N:1]([O-])=O.[Na+].[NH2:5][C:6]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:7]=1[C:8]([NH2:10])=[O:9]>O.Cl>[F:15][C:13]1[CH:12]=[CH:11][C:7]2[C:8](=[O:9])[NH:10][N:1]=[N:5][C:6]=2[CH:14]=1

Participants

5

Reactant 2

HCID 102410042-Amino-4-fluorobenzamideHCID 23668193Sodium Nitrite

Product 1

HCID 1361028587-Fluoro-3,4-dihydro-1,2,3-benzotriazin-4-oneYield 68.3%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent

Procedure

59.23 g (0.387 mol) of benzotriazol-1-ol, 65.776 ml (0.387 mol) of N-ethyldiisopropylamine and 74.15 g (0.387 mol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride were added successively at room temperature to a solution of 50.0 g (0.322 mol) of 2-amino-4-fluorobenzoic acid in 600 ml of dimethylformamide. 64.46 ml (0.451 mol) of ammonia in methanol (7 mol/l) were added dropwise with stirring, and the mixture was stirred for 18 hours. Water (2 l) and concentrated sodium chloride solution (0.5 l) were added to the batch. The mixture was extracted three times with ethyl acetate (0.75 l each time). The organic phase was dried over sodium sulfate, filtered, and the solvent was subsequently stripped off in a Rotavapor. The residue was triturated with 2-methoxy-2-methylpropane (0.2 l) and ligroin (0.1 l). The crystalline precipitate was filtered off with suction and dried in a drying cabinet, giving 44.5 g of 2-amino-4-fluorobenzamide as solid. 35.85 g (0.520 mol) of sodium nitrite in 75 ml of water were added dropwise at room temperature to a suspension of 44.5 g (0.289 mol) of 2-amino-4-fluorobenzamide in 1.4 l of hydrochloric acid (25%). The mixture was stirred for 2 hours with ice-cooling. The deposited precipitate was filtered off with suction, rinsed with water and dried at 60° C. in a vacuum drying cabinet, giving 32.58 g of 7-fluoro-3H-benzo[d]-1,2,3-triazin-4-one as solid; HPLC/MS (M+H)+=166; 1H NMR (300 MHz, DMSO) δ 8.32 (dd, J=8.8, 5.7, 1H), 7.87 (dd, J=9.0, 2.5, 1H), 7.64 (td, J=8.7, 2.5, 1H).

Workup

  1. temperaturecooling
  2. filtrationThe deposited precipitate was filtered off with suction
  3. washrinsed with water
  4. customdried at 60° C. in a vacuum
  5. customdrying cabinet

Sources & evidence

ORD record
ord-65552f224deb4a88a335b22ea230a9ae
Source dataset
uspto-grants-2015_11
Patent number
US09187469B2

Linked notes

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